11-78079609-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004549.6(NDUFC2):​c.136C>A​(p.Leu46Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L46V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NDUFC2
NM_004549.6 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0690
Variant links:
Genes affected
NDUFC2 (HGNC:7706): (NADH:ubiquinone oxidoreductase subunit C2) Involved in mitochondrial respiratory chain complex I assembly. Located in mitochondrion. Part of mitochondrial respiratory chain complex I. Implicated in nuclear type mitochondrial complex I deficiency. [provided by Alliance of Genome Resources, Apr 2022]
NDUFC2-KCTD14 (HGNC:42956): (NDUFC2-KCTD14 readthrough) This locus represents naturally occurring read-through transcription between the neighboring NDUFC2 (NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 2, 14.5kDa) and KCTD14 (potassium channel tetramerisation domain containing 14) genes on chromosome 11. The read-through transcripts share sequence identity with the upstream gene product and one variant has a frameshifted C-terminal region derived from the downstream gene exons. [provided by RefSeq, Feb 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.079265594).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NDUFC2NM_004549.6 linkc.136C>A p.Leu46Ile missense_variant 1/3 ENST00000281031.5 NP_004540.1 O95298-1A0A024R5K6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NDUFC2ENST00000281031.5 linkc.136C>A p.Leu46Ile missense_variant 1/31 NM_004549.6 ENSP00000281031.4 O95298-1
NDUFC2-KCTD14ENST00000612612.5 linkc.136C>A p.Leu46Ile missense_variant 1/42 ENSP00000478766.1 A0A087WUM3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1409690
Hom.:
0
Cov.:
66
AF XY:
0.00
AC XY:
0
AN XY:
696450
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
11
DANN
Benign
0.57
DEOGEN2
Benign
0.016
T;T;.;.;T;.;T;.;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0052
N
LIST_S2
Benign
0.51
T;T;T;T;T;T;T;T;T
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.079
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.81
.;L;.;.;.;.;.;.;.
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.52
N;N;.;.;N;N;N;N;N
REVEL
Benign
0.029
Sift
Benign
0.34
T;T;.;.;T;T;T;T;T
Sift4G
Benign
0.43
T;T;T;T;T;T;T;T;T
Polyphen
0.10
.;.;.;.;B;.;.;.;.
Vest4
0.15
MutPred
0.25
Loss of catalytic residue at L46 (P = 0.0599);Loss of catalytic residue at L46 (P = 0.0599);Loss of catalytic residue at L46 (P = 0.0599);Loss of catalytic residue at L46 (P = 0.0599);Loss of catalytic residue at L46 (P = 0.0599);Loss of catalytic residue at L46 (P = 0.0599);Loss of catalytic residue at L46 (P = 0.0599);Loss of catalytic residue at L46 (P = 0.0599);Loss of catalytic residue at L46 (P = 0.0599);
MVP
0.085
MPC
0.68, 0.69
ClinPred
0.080
T
GERP RS
-0.89
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.7
Varity_R
0.16
gMVP
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs8875; hg19: chr11-77790655; API